Navigation Links
Animal studies reveal new route to treating heart disease

Scientists at Johns Hopkins have shown in laboratory experiments in mice that blocking the action of a signaling protein deep inside the heart's muscle cells blunts the most serious ill effects of high blood pressure on the heart. These include heart muscle enlargement, scar tissue formation and loss of blood vessel growth.

Specifically, the Johns Hopkins team found that their intervention halted transforming growth factor beta (TGF-beta) secretion at a precise location called cell receptor type 2 in cardiac muscle cells. Blocking its action in this cell type forestalled pathways for hypertrophy, fibrosis, and angiogenesis by stopping the unbridled TGF-beta signaling, which is typically observed in heart failure, in all other non-muscle types of cells in blood vessels and fibrous tissue. However, blocking TGF-beta signaling in non-muscle cells did not stop disease progression.

In several dozen different experiments, using genetically altered mice or chemicals to selectively block different TGF-beta pathways, researchers were able to pinpoint where the signaling protein had its greatest impact on heart function and determine how its unimpeded activity promoted heart disease.

"Now that we know about the pivotal and specific bad roles played by TGF-beta in a common form of heart disease, we can try to mimic our lab experiments to develop cell-specific drug therapies that stop the chain reactions in the heart muscle at the TGF-beta type 2 cell receptor location," says senior study investigator and cardiologist, David Kass, M.D. Kass is a professor at the Johns Hopkins University School of Medicine and its Heart and Vascular Institute.

The Kass team study, to be published in the June edition of the Journal of Clinical Investigation, is believed to show the first evidence of how TGF-beta is stimulated differently by various cell types in the heart and which resulting pathways promote heart failure, the most common kind of heart disease. Nearly 6 million Americans are estimated to have the condition.

Kass says previous research showed TGF-beta played a mixed role in various heart diseases, reducing arterial inflammation in some while harming valve and blood vessel function in others, such as people with Marfan syndrome. Until now, however, no explanation existed as to why any of these differences occurred, which cells controlled the TGF-beta signal, and which enzymes are stimulated as a result.

In the new study, researchers also found that in mice with hypertension-induced disease, blocking TGF-beta type 2 cell receptor stopped activities of another kind of regulating protein, called TGF-beta activated kinase (TAK-1). Its activation appears to play a key role in heart enlargement and in secreting proteins tied to scarring, as well as others tied to blood vessel formation.

Researchers began the study with injections of TGF-beta neutralizing antibodies to see if they could rein in heart-failing TGF-beta signaling. But the disease got worse in mice whose hearts had induced high blood pressure, and TGF-beta signaling persisted inside the muscle cells even though it was suppressed in other cells in the heart. The action of two other kinds of proteins closely tied to TGF-beta was similarly split, with the activity of Smad proteins suppressed only outside muscle cells, while TAK-1 production continued. This led Kass and his team to investigate what was happening differently inside muscle cells.

Subsequent testing in mice selectively bred to lack either one of the two TGF-beta receptors in the muscle cells revealed that blocking only the TGF-beta type 2 cell receptor shut down both Smad and TAK-1 activity, stalling enlargement and scarring. Blocking only the TGF-beta type 1 receptor, however, failed to block TAK-1 activity, and disease-accelerating TGF-beta signaling persisted in non-muscle heart cells.

Researchers plan further tests in animals of chemicals that block TAK-1 as potential treatments for heart failure or other kinds of heart disease.


Contact: David March
Johns Hopkins Medical Institutions

Related medicine news :

1. New clues found linking larger animals to colder climates
2. Ghrelin mitigates liver fibrosis in animal models; regulates human fibrosis
3. ATTENTION: Pawty Animals Needed in Nashville, Tennessee
4. Second Dose of Gene Therapy for Inherited Blindness Proves Safe in Animal Studies
5. Promega - TOP srl Agreement Enables Live Animal Imaging for Cancer Studies
6. Delray Beach and Boca Raton Veterinarian Launches New Web Sites for Atlantic Animal Hospital
7. Gunther von Hagens BODY WORLDS of Animals Opening March 19 at the Neunkirchen Zoo
8. Scout's House™ Announces Nation's First Animal Physical Rehabilitation Therapy Consultation Service for Veterinarians
9. 'Animals' Keep Germs Away From Kids' Toothbrushes
10. Science Reveals Secrets of Animals Spots, Stripes
11. The effect of dietary supplements, acids and animal protein on gastrointestinal disorders
Post Your Comments:
(Date:11/27/2015)... ... November 27, 2015 , ... The print component ... Today in Atlanta, Dallas, New York, Minneapolis, South Florida, with a circulation of ... distributed nationally, through a vast social media strategy and across a network of ...
(Date:11/27/2015)... Wilmington, DE (PRWEB) , ... November 27, 2015 ... ... a member of the well-respected Microsoft Dynamics SL User Group (MSDSLUG). Recognized as ... is an independent group of Microsoft Dynamics SL software users, partners, industry experts ...
(Date:11/27/2015)... ... November 27, 2015 , ... CBD College is ... Health Education Programs (CAAHEP) awarded accreditation to its Diagnostic Medical Sonography program. CBD College ... as only one of twelve colleges and universities in the state of California make ...
(Date:11/27/2015)... , ... November 27, 2015 , ... ... center software Q-Suite, announces the incorporation of Asterisk 11 LTS (Long Term Support) ... supported Asterisk 11 LTS brings Q-Suite 5.10 up-to-date with a version of Asterisk ...
(Date:11/26/2015)... ... November 26, 2015 , ... ... Travel Representative. As a franchise owner, Somu now offers travelers, value and care ... wedding packages, private cruise sales, as well as, cabin upgrades and special amenities ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... November 26, 2015 ... the "Radioimmunoassay Market by Type (Reagents ... Industry, Academics, Clinical Diagnostic Labs), Application (Research, ... to 2020" report to their offering. ... the addition of the "Radioimmunoassay Market ...
(Date:11/25/2015)... WASHINGTON , Nov. 25, 2015  The ... Obstetricians and Gynecologists (ACOG), and the March of ... bipartisan Protecting Our Infants Act of 2015 ... the number of newborns born exposed to drugs, ... Since the bill,s introduction, all three organizations have ...
(Date:11/25/2015)... MELVILLE, N.Y. , Nov. 25, 2015  Henry ... products and services to office-based dental, medical and animal ... Dental (GNYDM) Meeting the Henry Schein ConnectDental® Pavilion ... industry,s broadest array of open solutions designed to help ... Click here for a schedule of ...
Breaking Medicine Technology: